tbuckley/cabot-search huggingface dataset:
The Effect of Lymphangiogenesis in Transplant Arteriosclerosis
Authors: Kai Chen, Rong Mou, Pengwei Zhu, Xiaodong Xu, Han Wang, Liujun Jiang, Yanhua Hu, Xiaosheng Hu, Liang Ma, Qingzhong Xiao, Qingbo Xu
Journal: Circulation (2022)

Transplant arteriosclerosis is a major complication in long-term survivors of heart transplantation. Increased lymph flow from donor heart to host lymph nodes has been reported to play a role in transplant arteriosclerosis, but how lymphangiogenesis affects this process is unknown.Vascular allografts were transplanted among various combinations of mice, including wild-type, Lyve1-CreERT2;R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency, Ccr2KO, Foxn1KO, and lghm/lghdKO mice. Whole-mount staining and 3-dimensional reconstruction identified lymphatic vessels within the grafted arteries. Lineage tracing strategies delineated the cellular origin of lymphatic endothelial cells. Adeno-associated viral vectors and a selective inhibitor were used to regulate lymphangiogenesis.Lymphangiogenesis within allograft vessels began at the anastomotic sites and extended from preexisting lymphatic vessels in the host. Tertiary lymphatic organs were identified in transplanted arteries at the anastomotic site and lymphatic vessels expressing CCL21 (chemokine [C-C motif] ligand 21) were associated with these immune structures. Fibroblasts in the vascular allografts released VEGF-C (vascular endothelial growth factor C), which stimulated lymphangiogenesis into the grafts. Inhibition of VEGF-C signaling inhibited lymphangiogenesis, neointima formation, and adventitial fibrosis of vascular allografts. These studies identified VEGF-C released from fibroblasts as a signal stimulating lymphangiogenesis extending from the host into the vascular allografts.Formation of lymphatic vessels plays a key role in the immune response to vascular transplantation. The inhibition of lymphangiogenesis may be a novel approach to prevent transplant arteriosclerosis.
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression
Authors: Emmanuelle Born, Larissa Lipskaia, Marielle Breau, Amal Houssaini, Delphine Beaulieu, Elisabeth Marcos, Remi Pierre, Marcio Do Cruzeiro, Marine Lefevre, Genevieve Derumeaux, Dmitry V. Bulavin, Marion Delcroix, Rozenn Quarck, Virinder Reen, Jesus Gil, David Bernard, Jean-Michel Flaman, Serge Adnot, Shariq Abid
Journal: Circulation (2022)

Background: Senescent cells (SCs) are involved in proliferative disorders, but their role in pulmonary hypertension remains undefined. We investigated SCs in patients with pulmonary arterial hypertension and the role of SCs in animal pulmonary hypertension models. Methods: We investigated senescence (p16, p21) and DNA damage (γ-H2AX, 53BP1) markers in patients with pulmonary arterial hypertension and murine models. We monitored p16 activation by luminescence imaging in p16-luciferase (p16 LUC/+ ) knock-in mice. SC clearance was obtained by a suicide gene (p16 promoter–driven killer gene construct in p16-ATTAC mice), senolytic drugs (ABT263 and cell-permeable FOXO4-p53 interfering peptide [FOXO4-DRI]), and p16 inactivation in p16 LUC/LUC mice. We investigated pulmonary hypertension in mice exposed to normoxia, chronic hypoxia, or hypoxia+Sugen, mice overexpressing the serotonin transporter (SM22-5-HTT + ), and rats given monocrotaline. Results: Patients with pulmonary arterial hypertension compared with controls exhibited high lung p16, p21, and γ-H2AX protein levels, with abundant vascular cells costained for p16, γ-H2AX, and 53BP1. Hypoxia increased thoracic bioluminescence in p16 LUC/+ mice. In wild-type mice, hypoxia increased lung levels of senescence and DNA-damage markers, senescence-associated secretory phenotype components, and p16 staining of pulmonary endothelial cells (P-ECs, 30% of lung SCs in normoxia), and pulmonary artery smooth muscle cells. SC elimination by suicide gene or ABT263 increased the right ventricular systolic pressure and hypertrophy index, increased vessel remodeling (higher dividing proliferating cell nuclear antigen–stained vascular cell counts during both normoxia and hypoxia), and markedly decreased lung P-ECs. Pulmonary hemodynamic alterations and lung P-EC loss occurred in older p16 LUC/LUC mice, wild-type mice exposed to Sugen or hypoxia+Sugen, and SM22-5-HTT + mice given either ABT263 or FOXO4-DRI, compared with relevant controls. The severity of monocrotaline-induced pulmonary hypertension in rats was decreased slightly by ABT263 for 1 week but was aggravated at 3 weeks, with loss of P-ECs. Conclusions: Elimination of senescent P-ECs by senolytic interventions may worsen pulmonary hemodynamics. These results invite consideration of the potential impact on pulmonary vessels of strategies aimed at controlling cell senescence in various contexts.
Development of Mitochondria Targeting AIE‐Active Cyclometalated Iridium Complexes as Potent Antimalarial Agents
Authors: Geeta Kumari, Ajay Gupta, Raj Kumar Sah, Aryan Gautam, Monika Saini, Aashima Gupta, Akhilesh K. Kushawaha, Shailja Singh, Pijus K. Sasmal
Journal: Advanced Healthcare Materials (2022)

The emergence of resistance to conventional antimalarial treatments remains a major cause for concern. New drugs that target the distinct development stages of Plasmodium parasites are required to address this risk. Herein, water-soluble aggregation-induced emission active cyclometalated iridium(III) polypyridyl complexes (Ir1-Ir12) are developed for the elimination of malaria parasites. Remarkably, these complexes show potent antimalarial activity in low nanomolar range against 3D7 (chloroquine and artemisinin sensitive strain), RKL9 (chloroquine resistant strain), and R539T (artemisinin resistant strains) strains of Plasmodium falciparum with faster killing rate of malaria parasites. Concomitantly, these complexes exhibit efficient in vivo antimalarial activity against both the asexual and gametocyte stages of Plasmodium berghei malaria parasite, suggesting promising transmission-blocking potential. The complexes tend to localize into mitochondria of P. falciparum determined by image and cell-based assay. The mechanistic studies reveal that these complexes exert their antimalarial activity by increasing reactive oxygen species levels and disrupting its mitochondrial membrane potential. Furthermore, the mitochondrial-dependent antimalarial activity of these complexes is confirmed in yeast model. Thus, this study for the first time highlights the potential role of targeting P. falciparum mitochondria by iridium complexes in discovering and developing the next-generation antimalarial agents for treating multidrug resistant malaria parasites.
Flexible Skin Patch Enabled Tumor Hybrid Thermophysical Therapy and Adaptive Antitumor Immune Response
Authors: Xuyang Sun, Tao Wu, Minghui Duan, Bo Yuan, Xiyu Zhu, Hongzhang Wang, Jing Liu
Journal: Advanced Healthcare Materials (2022)

Innovations on materials and technologies have greatly promoted the rapid development of wearable electronics from disease diagnosis to therapeutics. For superficial skin tumors, skin-attachable patches possess the advantages of minimally invasive property, alleviative side effects, and high efficiency. The development of noninvasive techniques and devices is still in urgent demands. Here, a flexible skin patch fabricated through a facile preparation method is reported for noninvasive hybrid thermophysical therapy and adaptative immune function enhancement. The liquid metal enabled skin patch is demonstrated with high conductivity, certain stability, biocompatibility, and an enhanced adhesive merit on skin surfaces for cryoablation therapy and magnetic hyperthermia therapy. The skin patch exhibits remarkably conformable heating and cooling performance toward the treatment of 4T1 breast tumors. The magnetic resonance images also indicate the significant tumor ablation effect. Interestingly, a relatively stable proportion of both CD8+ T and CD4+ T cells in the peripheral blood is identified after tumor therapy in comparison with the decreased trend in the untreated group, representing an efficient antitumor immune response induced by the skin patch. The developed skin patch would provide a promising noninvasive approach for tumor therapies by direct tumor destruction and maintenance of the antitumor immune response.
Nanoparticles-based phototherapy systems for cancer treatment: Current status and clinical potential
Authors: Jiachen Li, Shiqi Wang, Flavia Fontana, Christos Tapeinos, Mohammad-Ali Shahbazi, Huijie Han, Hélder A. Santos
Journal: Bioactive Materials (2022)

Remarkable progress in phototherapy has been made in recent decades, due to its non-invasiveness and instant therapeutic efficacy. In addition, with the rapid development of nanoscience and nanotechnology, phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research, especially in cancer. In this review, first we briefly introduce the history of phototherapy, and the mechanisms of phototherapy in cancer treatment. Then, we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof. Finally, we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications, aiming to predict future research directions in this field. Our review is a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology, nanoscience and cancer.
Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes
Authors: Chengran Yang, Anne M. Fagan, Richard J. Perrin, Herve Rhinn, Oscar Harari, Carlos Cruchaga
Journal: Genome Medicine (2022)

Human proteins are widely used as drug targets. Integration of large-scale protein-level genome-wide association studies (GWAS) and disease-related GWAS has thus connected genetic variation to disease mechanisms via protein. Previous proteome-by-phenome-wide Mendelian randomization (MR) studies have been mainly focused on plasma proteomes. Previous MR studies using the brain proteome only reported protein effects on a set of pre-selected tissue-specific diseases. No studies, however, have used high-throughput proteomics from multiple tissues to perform MR on hundreds of phenotypes.
cDC1-derived IL-27 regulates small intestinal CD4+ T cell homeostasis in mice
Authors: Fatemeh Ahmadi, Fredrik Junghus, Christian Ashworth, Amanda Lappalainen, Urs Mörbe, Knut Kotarsky, William W. Agace
Journal: The Journal of Experimental Medicine (2022)

The small intestinal lamina propria contains large numbers of IFNγ-producing T helper (Th1) cells that play important roles in intestinal homeostasis and host defense, but the mechanisms underlying their development remain poorly understood. Here, we demonstrate that Th1 cells accumulate in the SI-LP after weaning and are maintained there long term. While both Th17 and Th1 cell accumulation in the SI-LP was microbiota dependent, Th1 cell accumulation uniquely required IL-27 and MHCII expression by cDC1. This reflected a requirement for IL-27 signaling in the priming of Th1 cells rather than for their maintenance once in the mucosa. cDC1-derived IL-27 was essential for maintaining the Th1-Th17 balance within the SI-LP, and in its absence, remaining Th1 cells expressed enhanced levels of Th17 signature genes. In conclusion, we identify cDC1-derived IL-27 as a key regulator of SI-LP Th1-Th17 cell homeostasis.
Pollinator Deficits, Food Consumption, and Consequences for Human Health: A Modeling Study
Authors: Matthew R. Smith, Nathaniel D. Mueller, Marco Springmann, Timothy B. Sulser, Lucas A. Garibaldi, James Gerber, Keith Wiebe, Samuel S. Myers
Journal: Environmental Health Perspectives (2022)

Animal pollination supports agricultural production for many healthy foods, such as fruits, vegetables, nuts, and legumes, that provide key nutrients and protect against noncommunicable disease. Today, most crops receive suboptimal pollination because of limited abundance and diversity of pollinating insects. Animal pollinators are currently suffering owing to a host of direct and indirect anthropogenic pressures: land-use change, intensive farming techniques, harmful pesticides, nutritional stress, and climate change, among others.We aimed to model the impacts on current global human health from insufficient pollination via diet.We used a climate zonation approach to estimate current yield gaps for animal-pollinated foods and estimated the proportion of the gap attributable to insufficient pollinators based on existing research. We then simulated closing the "pollinator yield gaps" by eliminating the portion of total yield gaps attributable to insufficient pollination. Next, we used an agriculture-economic model to estimate the impacts of closing the pollinator yield gap on food production, interregional trade, and consumption. Finally, we used a comparative risk assessment to estimate the related changes in dietary risks and mortality by country and globally. In addition, we estimated the lost economic value of crop production for three diverse case-study countries: Honduras, Nepal, and Nigeria.Globally, we calculated that 3%-5% of fruit, vegetable, and nut production is lost due to inadequate pollination, leading to an estimated 427,000 (95% uncertainty interval: 86,000, 691,000) excess deaths annually from lost healthy food consumption and associated diseases. Modeled impacts were unevenly distributed: Lost food production was concentrated in lower-income countries, whereas impacts on food consumption and mortality attributable to insufficient pollination were greater in middle- and high-income countries with higher rates of noncommunicable disease. Furthermore, in our three case-study countries, we calculated the economic value of crop production to be 12%-31% lower than if pollinators were abundant (due to crop production losses of 3%-19%), mainly due to lost fruit and vegetable production.According to our analysis, insufficient populations of pollinators were responsible for large present-day burdens of disease through lost healthy food consumption. In addition, we calculated that low-income countries lost significant income and crop yields from pollinator deficits. These results underscore the urgent need to promote pollinator-friendly practices for both human health and agricultural livelihoods. https://doi.org/10.1289/EHP10947.
Inhibition of S100A8/A9 ameliorates renal interstitial fibrosis in diabetic nephropathy
Authors: Lei Du, Yibing Chen, Jiasen Shi, Xiujuan Yu, Jieling Zhou, Xue Wang, Liu Xu, Junjie Liu, Jian Gao, Xiaoke Gu, Tao Wang, Zeyuan Yin, Chenglin Li, Meng Yan, Jianyun Wang, Xiaoxing Yin, Qian Lu
Journal: Metabolism (2022)
Global Burden of Cardiovascular Diseases and Risks Collaboration, 1990-2021
Authors: Megan Lindstrom, Nicole DeCleene, Henry Dorsey, Valentin Fuster, Catherine O. Johnson, Kate E. LeGrand, George A. Mensah, Christian Razo, Benjamin Stark, Justine Varieur Turco, Gregory A. Roth
Journal: Journal of the American College of Cardiology (2022)
Real-world evidence on atopic dermatitis: Baseline characteristics and predictors of treatment choice in the TARGET cohort
Authors: Katrina Abuabara, Lawrence F. Eichenfield, Robert Bissonnette, Jonathan I. Silverberg, Jerry Bagel, Emma Guttman-Yassky, Diamant Thaci, Eric L. Simpson, John E. Harris, James Krueger, Daniela E. Myers, Amy Gamelli, Marina Milutinovic, Anne Parneix, Julie M. Crawford, Janet S. Hildebrand, Breda Munoz, Amy S. Paller
Journal: Journal of the American Academy of Dermatology (2022)
Noninvasive Assessment of Postoperative Disease Recurrence in Crohn’s Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease
Authors: Federica Furfaro, Ferdinando D’Amico, Alessandra Zilli, Vincenzo Craviotto, Annalisa Aratari, Cristina Bezzio, Antonino Spinelli, Daniela Gilardi, Simona Radice, Simone Saibeni, Claudio Papi, Laurent Peyrin-Biroulet, Silvio Danese, Gionata Fiorino, Mariangela Allocca
Journal: Clinical Gastroenterology and Hepatology (2022)
Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial
Authors: Paula Ghaneh, Daniel Palmer, Silvia Cicconi, Richard Jackson, Christopher Michael Halloran, Charlotte Rawcliffe, Rajaram Sripadam, Somnath Mukherjee, Zahir Soonawalla, Jonathan Wadsley, Ahmed Al-Mukhtar, Euan Dickson, Janet Graham, Long Jiao, Harpreet S Wasan, Iain S Tait, Andreas Prachalias, Paul Ross, Juan W Valle, Derek A O'Reilly, Bilal Al-Sarireh, Sarah Gwynne, Irfan Ahmed, Kate Connolly, Kein-Long Yim, David Cunningham, Thomas Armstrong, Caroline Archer, Keith Roberts, Yuk Ting Ma, Christoph Springfeld, Christine Tjaden, Thilo Hackert, Markus W Büchler, John P Neoptolemos
Journal: The Lancet. Gastroenterology & hepatology (2022)
Re: George J. Netto, Mahul B. Amin, Eva M. Compérat, et al. Prostate Adenocarcinoma Grade Group 1: Rationale for Retaining a Cancer Label in the 2022 World Health Organization Classification. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.09.015
Authors: Alessia Cimadamore, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
Journal: European Urology (2022)
Disease outbreaks in Pakistan, Lebanon, and Syria
Authors: Priya Venkatesan
Journal: The Lancet Microbe (2022)

Years of economic crises, wars, and environmental disasters have resulted in escalating outbreaks of infectious diseases in countries that are ill-equipped to deal with such public health emergencies. Following the devastating floods in Pakistan in June, 2022, there has been a huge and rapid increase in cases of malaria and dengue. And a fast-spreading cholera outbreak is ongoing in war-torn Syria and, for the first time in 30 years, in Lebanon.
The deubiquitinating enzyme 13 retards non-alcoholic steatohepatitis via blocking inactive rhomboid protein 2-dependent pathway
Authors: Minxuan Xu, Jun Tan, Liancai Zhu, Chenxu Ge, Wei Dong, Xianling Dai, Qin Kuang, Shaoyu Zhong, Lili Lai, Chao Yi, Qiang Li, Deshuai Lou, Linfeng Hu, Xi Liu, Gang Kuang, Jing Luo, Jing Feng, Bochu Wang
Journal: Acta Pharmaceutica Sinica B (2022)

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the
Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer
Authors: Ramya Dhandapani, Swaminathan Sethuraman, Uma Maheswari Krishnan, Anuradha Subramanian
Journal: Acta Pharmaceutica Sinica B (2022)

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.
Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study
Authors: Rohit Loomba, Eric J Lawitz, Juan Pablo Frias, Grisell Ortiz-Lasanta, Lars Johansson, Bridgette Boggess Franey, Linda Morrow, Moti Rosenstock, Cynthia L Hartsfield, Chao-Yin Chen, Leo Tseng, R Will Charlton, Hank Mansbach, Maya Margalit
Journal: The Lancet. Gastroenterology & hepatology (2022)
Viral dynamics in patients with monkeypox infection: a prospective cohort study in Spain
Authors: Clara Suñer, Maria Ubals, Eloy José Tarín-Vicente, Adrià Mendoza, Andrea Alemany, Águeda Hernández-Rodríguez, Cristina Casañ, Vicente Descalzo, Dan Ouchi, Aurélien Marc, Àngel Rivero, Pep Coll, Xènia Oller, José Miguel Cabrera, Martí Vall-Mayans, María Dolores Folgueira, María Ángeles Melendez, Manuel Agud-Dios, Elena Gil-Cruz, Alexia Paris de Leon, Aída Ramírez Marinero, Vira Buhiichyk, Cristina Galván-Casas, Roger Paredes, Nuria Prat, Maria-Rosa Sala Farre, Josep Maria Bonet-Simó, Magí Farré, Pablo L Ortiz-Romero, Bonaventura Clotet, Vicente García-Patos, Jordi Casabona, Jeremie Guedj, Pere-Joan Cardona, Ignacio Blanco, Michael Marks, Oriol Mitjà, José Ramón Santos, Lucía Bailón, Susana Benet, Jorge Arroyo Andres, Lorena Calderón Lozano, María Carrasco Díaz, Carla Budria Serrano, Enola Crespillo Galán, Ana Isabel Parra Manzano, Pamela Nef Rabadán, Laura Muntané, Cristina Sánchez-Lafuente Doncel, Yesinei Marina Marrero Pueo, Aroa Muñoz Quinto, Marlon Acosta, Patricia Alvarez, Maider Arando, Jorge N García, Arnau Monforte, Yolanda Maltas Hidalgo, Ramona Hervas Perez, Laura Clotet Romero
Journal: The Lancet Infectious Diseases (2022)
Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era
Authors: Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril
Journal: Clinical Gastroenterology and Hepatology (2022)